The long-term objective of this research is to relate visual deficits in patients to the underlying cellular pathophysiology. The proposed research uses new psychophysical measures for monitoring cell dysfunction, and quantitative modeling to relate glaucomatous visual defects with ganglion cell damage. These aims will lay the foundation for development of new forms of perimetry. The Specific Aims are: 1) To develop a clinically useful version of a new method for evaluating ganglion cell dysfunction. Over the past decade a new functional technique has been developed in terms of saturation of ganglion cell spike generation, and has been applied to the study of foveal dysfunction. The proposed research will develop a version of this technique for evaluating dysfunction throughout the visual field. The clinical version will be used to follow patients in Specific Aim 2, and will be modeled in Specific Aim 4. 2) To follow patients being treated for glaucoma, using methods with sufficient precision to detect improvement in visual function. We have demonstrated that test-retest variability can be reduced by using stimuli for which cortical mechanisms summate responses of large numbers of ganglion cells. These stimuli, along with the method developed in Specific Aim 1, will be used to monitor visual function in glaucomatous defects. In this Aim we will use these methods to follow patients undergoing treatment for glaucoma, in order to evaluate the potential role of ganglion cell dysfunction in determining depth of defect. 3) To evaluate structural and functional data on glaucomatous defects using quantitative modeling of effects of ganglion cell death and dysfunction. Functional data for conventional perimetry and for our new tests will be compared with structural measures of ganglion cell loss, to more precisely define the potential roles of cell dysfunction and cell death in structure/function comparisons. 4) To extend our quantitative modeling by analyzing potential effects of neural noise in terms of population dynamics and spike train analysis. We will use both neurometric analysis of macaque ganglion cell spike trains and simulation of population dynamics to incorporate physiologically plausible sources of neural noise and distinguish between decreased sensitivity of ganglion cells vs. increased neural noise, and provide an improved understanding of the effects of different aspects of cellular pathophysiology.